Projects per year
BACKGROUND: The mammalian thalamus relays sensory information from the periphery to the cerebral cortex for cognitive processing via the thalamocortical tract. The thalamocortical tract forms during embryonic development controlled by mechanisms that are not fully understood. Beta-catenin is a nuclear and cytosolic protein that transduces signals from secreted signalling molecules to regulate both cell motility via the cytoskeleton and gene expression in the nucleus. In this study we tested whether beta-catenin is likely to play a role in thalamocortical connectivity by examining its expression and activity in developing thalamic neurons and their axons. RESULTS: At embryonic day (E)15.5, the time when thalamocortical axonal projections are forming, we found that the thalamus is a site of particularly high beta-catenin mRNA and protein expression. As well as being expressed at high levels in thalamic cell bodies, beta-catenin protein is enriched in the axons and growth cones of thalamic cells and its growth cone concentration is sensitive to Netrin-1. Using mice carrying the beta-catenin reporter BAT-gal we find high levels of reporter activity in the thalamus. Further, Netrin-1 induces BAT-gal reporter expression and upregulates levels of endogenous transcripts encoding beta-actin and L1 proteins in cultured thalamic cells. We found that beta-catenin mRNA is enriched in thalamic axons and its 3'UTR is phylogenetically conserved and is able to direct heterologous mRNAs along the thalamic axon, where they can be translated. CONCLUSION: We provide evidence that beta-catenin protein is likely to be an important player in thalamocortcial development. It is abundant both in the nucleus and in the growth cones of post-mitotic thalamic cells during the development of thalamocortical connectivity and beta-catenin mRNA is targeted to thalamic axons and growth cones where it could potentially be translated. Beta-catenin is involved in transducing the Netrin-1 signal to thalamic cells suggesting a mechanism by which Netrin-1 guides thalamocortical development.
1/01/09 → 30/06/14